TY - JOUR
T1 - Disruption of inducible 6-phosphofructo-2-kinase impairs the suppressive effect of PPARγ activation on diet-induced intestine inflammatory response
AU - Guo, Xin
AU - Li, Honggui
AU - Xu, Hang
AU - Halim, Vera
AU - Thomas, Laura N.
AU - Woo, Shih Lung
AU - Huo, Yuqing
AU - Chen, Y. Eugene
AU - Sturino, Joseph M.
AU - Wu, Chaodong
N1 - Funding Information:
This work was supported, in whole or in part, by NIH HL105114 (Y.E.C.) and by ADA grant 1-10-JF-54 and AHA 12BGIA9050003 (to C.W.).
Funding Information:
This work was supported in part by William W. Allen Foundation (PI: C.W.; Endowment Recipient: Joanne Lupton), American Diabetes Association grant ( 1-10-JF-54 ) and American Heart Association grant (12BGIA9050003) (to C.W.) and National Institutes of Health ( HL105114 to Y.E.C.).
PY - 2013/5
Y1 - 2013/5
N2 - PFKFB3 is a target gene of peroxisome proliferator-activated receptor gamma (PPARγ) and encodes for inducible 6-phosphofructo-2-kinase (iPFK2). As a key regulatory enzyme that stimulates glycolysis, PFKFB3/iPFK2 links adipocyte metabolic and inflammatory responses. Additionally, PFKFB3/iPFK2 is involved in the effect of active PPARγ on suppressing overnutrition-induced adipose tissue inflammatory response, which accounts for the insulin-sensitizing and antidiabetic effects of PPARγ activation. Using PFKFB3/iPFK2-disrupted mice, the present study investigated the role of PFKFB3/iPFK2 in regulating overnutrition-associated intestine inflammatory response and in mediating the effects of PPARγ activation. In wild-type mice, intestine PFKFB3/iPFK2 was increased in response to high-fat diet (HFD) feeding compared with that in mice fed a low-fat diet. However, intestine PFKFB3/iPFK2 was decreased in PFKFB3/iPFK2-disrupted mice and did not respond to HFD feeding. Furthermore, on an HFD, PFKFB3/iPFK2-disrupted mice displayed a significant increase in major intestine proinflammatory indicators such as toll-like receptor 4 expression, c-Jun N-terminal kinase 1 and nuclear factor kappa B phosphorylation, and proinflammatory cytokine expression compared with wild-type littermates. Upon treatment with rosiglitazone, an agonist of PPARγ, intestine proinflammatory indicators were markedly decreased in wild-type mice, but to a much lesser degree in PFKFB3/iPFK2-disrupted mice. Overall, the status of HFD-induced intestine inflammatory response in all treated mice correlated inversely with systemic insulin sensitivity, indicated by the homeostasis model assessment of insulin resistance data. Together, these results suggest that PFKFB3/iPFK2 is critically involved in the effect of PPARγ activation on suppressing diet-induced intestine inflammatory response.
AB - PFKFB3 is a target gene of peroxisome proliferator-activated receptor gamma (PPARγ) and encodes for inducible 6-phosphofructo-2-kinase (iPFK2). As a key regulatory enzyme that stimulates glycolysis, PFKFB3/iPFK2 links adipocyte metabolic and inflammatory responses. Additionally, PFKFB3/iPFK2 is involved in the effect of active PPARγ on suppressing overnutrition-induced adipose tissue inflammatory response, which accounts for the insulin-sensitizing and antidiabetic effects of PPARγ activation. Using PFKFB3/iPFK2-disrupted mice, the present study investigated the role of PFKFB3/iPFK2 in regulating overnutrition-associated intestine inflammatory response and in mediating the effects of PPARγ activation. In wild-type mice, intestine PFKFB3/iPFK2 was increased in response to high-fat diet (HFD) feeding compared with that in mice fed a low-fat diet. However, intestine PFKFB3/iPFK2 was decreased in PFKFB3/iPFK2-disrupted mice and did not respond to HFD feeding. Furthermore, on an HFD, PFKFB3/iPFK2-disrupted mice displayed a significant increase in major intestine proinflammatory indicators such as toll-like receptor 4 expression, c-Jun N-terminal kinase 1 and nuclear factor kappa B phosphorylation, and proinflammatory cytokine expression compared with wild-type littermates. Upon treatment with rosiglitazone, an agonist of PPARγ, intestine proinflammatory indicators were markedly decreased in wild-type mice, but to a much lesser degree in PFKFB3/iPFK2-disrupted mice. Overall, the status of HFD-induced intestine inflammatory response in all treated mice correlated inversely with systemic insulin sensitivity, indicated by the homeostasis model assessment of insulin resistance data. Together, these results suggest that PFKFB3/iPFK2 is critically involved in the effect of PPARγ activation on suppressing diet-induced intestine inflammatory response.
KW - Inducible 6-phosphofructo-2-kinase
KW - Inflammatory response
KW - Intestine
KW - Overnutrition
KW - PPARγ
UR - http://www.scopus.com/inward/record.url?scp=84876813443&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876813443&partnerID=8YFLogxK
U2 - 10.1016/j.jnutbio.2012.04.007
DO - 10.1016/j.jnutbio.2012.04.007
M3 - Article
C2 - 22841546
AN - SCOPUS:84876813443
SN - 0955-2863
VL - 24
SP - 770
EP - 775
JO - Journal of Nutritional Biochemistry
JF - Journal of Nutritional Biochemistry
IS - 5
ER -